Retinal Toxicity from Hydroxychloroquine

Plaquenil® tablets contain 200mg hydroxychloroquine sulfate and are used in the treatment of malaria, discoid and systemic lupus erythematosus, and rheumatoid arthritis. Plaquenil® is classified as a disease-modifying antirheumatic drug (DMAD), although the exact mechanism of action is not known.

Retinal toxicity from hydroxychloroquine is quite rare, considering the number of people who use Plaquenil®. For those patients who develop retinal toxicity, permanent vision loss may result, even after stopping the medication. Evidence suggests that retinal toxicity incidence depends on both dosage volume and duration; the majority of reported cases have occurred at dosages greater than 6.5mg per kilogram (of body weight) per day in patients who used Plaquenil® for more than five years1. With more than one million patients using this medication, less than 20 cases have occurred in doses less than 6.5 mg/kg/day, and all have occurred with greater than five years of usage1.

The typical dosage of Plaquenil® is either 200mg or 400mg per day. Two hundred milligrams per day puts anyone under 68 pounds at risk for retinal toxicity, and 400mg per days puts anyone under 135 pounds at risk.2 So, 200mg of Plaquenil per day is a safe dosage for almost all adults, unless they are particularly diminutive or have other risk factors, such as kidney failure or liver disease.2-3

Bull's Eye maculopathy; courtesy of IU School of Optometry

Even though retinal toxicity from hydroxychloroquine is exceedingly rare, clinicians still routinely screen patients who are on hydroxychloroquine. In 2002, the American Academy of Ophthalmology (AAO) established recommendations for monitoring patients who take hydroxychloroquine.1 AAO officials classified hydroxychloroquine patients into a low-risk group (patients who have used less than 6.5mg per kilogram per day for fewer than five years) and a high-risk group (patients who have used larger doses; have taken the medicationfor longer than five years; have other risk factors, such as a high body fat level, concomitant kidney or liver disease or concomitant retinal disease; or are older than 60 years of age).

For patients in the low-risk category, the AAO recommends that no additional special testing is needed for five years; however, an annual eye examination is recommended for patients in the high-risk category. It should be emphasized that these are the minimal follow up guidelines.

All patients who are starting hydroxychloroquine should have a baseline eye exam within the first year of starting treatment to include dilated fundus exam, testing of central visual field by either an Amsler grid or an automated threshold 10-2 central visual field.1 There has been some debate as to what the best parameters are for performing threshold central visual field testing. Some investigators have advocated using a red stimulus, with the belief that red may be more sensitive to detect early toxicity. The problem with the red stimulus is that there is no normative data base available to compare the patients, and there tends to be an increase in “false positive” responses. For these reasons, many clinicians continue to follow their patients using a white stimulus. Red-green color defects have been described in patients with early hydroxychloroquine toxicity, so color vision testing is also recommended for baseline testing as well as follow up testing.